Pheochromocytoma is usually characterized by a marked increase in peripheral catecholamine secretion. Whether this is accompanied by an alteration in central sympathetic drive has not been clarified. In 6 patients with adrenal pheochromocytoma (mean+/-SEM age, 49. 3+/-7.2 years), we measured systolic and diastolic blood pressure (photoplethysmographic device), heart rate (ECG), venous plasma catecholamines (high-performance liquid chromatography), and postganglionic muscle sympathetic nerve activity (microneurography) before and 78.3+/-13 days after surgical removal of the tumor. In each experimental session, measurements were performed during (1) a 60-minute resting period to compare several values of sympathetic nerve traffic at similar blood pressures before and after surgery and (2) voluntary end-expiratory apnea, ie, a maneuver inducing sympathetic activation. Tumor removal significantly (P<0.05 at least) reduced plasma catecholamines, blood pressure, and heart rate. In contrast, muscle sympathetic nerve activity was significantly (P<0.01) increased, both when quantified as bursts per minute (from 28.1+/-5.7 to 54.3+/-7.5) and as bursts per 100 heartbeats (from 33. 4+/-5.6 to 65.1+/-6.5). This was also the case when data were evaluated in periods of 2 experimental sessions characterized by similar diastolic blood pressure values. The apnea maneuver induced sympathetic nerve traffic responses that were significantly (P<0.05) greater after surgery than before surgery. These data provide the first direct evidence that in pheochromocytoma central sympathetic outflow is markedly reduced and that this reduction cannot be ascribed to a reflex inhibitory response to elevated blood pressures. It is likely that this sympathoinhibition is rather due to a central depression of sympathetic outflow induced by high circulating catecholamines.